Rethinking Risk Stratification for Acute Lymphoblastic Leukemia

Researchers at St. Jude Children’s Research Hospital have integrated genomic analysis with minimal residual disease (MRD) assessment to improve prediction of treatment response in pediatric patients with acute lymphoblastic leukemia (ALL). Up until now, medical centers have faced barriers to adopting this integrated approach. “Many are not able to perform both assays in house – especially the comprehensive genomic analyses,” says Ching-Hon Pui, Chair of St. Jude’s oncology department. “Even if they have the expertise, they need to perform the assays in a CLIA-certified laboratory and conduct the analyses in real time so they can be used clinically.”

In the study, the team found that high-hyperdiploid and DUX4-rearranged B-ALL had the best five-year event-free survival rates; BCR-ABL1, BCR-ABL1-like, ETV6-RUNX1-like, and KMT2A-rearranged ALL had the worst. This was surprising to Pui. “Some investigators thought the ETV6-RUNX1-like subtype should have excellent outcomes because it shares the gene expression of the ETV6-RUNX1 subtype – the most favorable subtype,” he says. “But, based on our data, this subtype is actually unfavorable. Another notable finding is the excellent outcome of DUX4-rearranged ALL despite high rates of MRD positivity early in therapy.”

When asked about how the findings will enhance the day-to-day work of pathologists working with pediatric cancers, Pui notes the positive effect pathologists can have on patients. “The cure and quality of life of our children with ALL are affected tremendously by pathologists,” he says. “Many children inherited these cancer susceptibility genes – and so their family members will also require the expertise of our pathologists who perform germline genomic studies.”

How long will it take until this integrated approach becomes available in the clinic?  “We are routinely testing for more than 20 genetic subtypes in both our ALL patients at St. Jude and those participating in our clinical trial in several other collaborative medical centers – and using the information for risk-directed treatment,” says Pui. “Other medical centers are screening their patients for selected high-risk subtypes and some can also perform comprehensive genomic analysis. I hope that, within the next three to five years, those tests will be readily available for all patients.”